Direct visualization of cross-reactive effector and memory allo-specific CD8 T cells generated in response to viral infections

UMMS Affiliation

Department of Pathology; Department of Medicine, Division of Diabetes

Publication Date


Document Type



Animals; CD8-Positive T-Lymphocytes; Cell Line; Cells, Cultured; *Cytotoxicity Tests, Immunologic; Epitopes, T-Lymphocyte; Immune Tolerance; Immunity, Natural; Immunodominant Epitopes; *Immunologic Memory; Interferon Type II; Isoantigens; Lymphocyte Activation; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Knockout; Pichinde virus; Receptors, Antigen, T-Cell, alpha-beta; Skin Transplantation; T-Lymphocyte Subsets; Tumor Cells, Cultured


Life Sciences | Medicine and Health Sciences


CD8 T cell cross-reactivity between heterologous viruses has been shown to provide protective immunity, induce immunopathology, influence the immunodominance of epitope-specific T cell responses, and shape the overall memory population. Virus infections also induce cross-reactive allo-specific CTL responses. In this study, we quantified the allo-specific CD8 T cells elicited by infection of C57BL/6 (B6) mice with lymphocytic choriomeningitis virus (LCMV). Cross-reactive LCMV-specific CD8 T cells were directly visualized using LCMV peptide-charged MHC tetramers to costain T cells that were stimulated to produce intracellular IFN-gamma in response to allogeneic target cells. The cross-reactivity between T cells specific for LCMV and allogeneic Ags was broad-based, in that it involved multiple LCMV-derived peptides, but there were distinctive patterns of reactivity against allogeneic cells with different haplotypes. Experiments indicated that this cross-reactivity was not due to the expression of two TCR per cell, and that the patterns of allo-reactivity changed during sequential infection with heterologous viruses. The allo-specific CD8 T cells generated by LCMV infection were maintained at relatively high frequencies in the memory pool, indicating that memory allo-specific CD8 T cell populations can arise as a consequence of viral infections. Mice previously infected with LCMV and harboring allo-specific memory T cells were refractory to the induction of tolerance to allogeneic skin grafts.

DOI of Published Version



J Immunol. 2003 Apr 15;170(8):4077-86.

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

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Link to Article in PubMed

PubMed ID